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Wednesday, April 18, 2018

Columbus: A clinically relevant “liquid biopsy” test can be used to profile
cancer genomes from blood and predict survival outcomes for patients
with metastatic triple negative breast cancer (TNBC), according to new
research published by a multi-institutional team of researchers with The Ohio State University Comprehensive Cancer Center — Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James), the Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard.
Although TNBC represents just 10-15 percent of all breast cancer
diagnoses, the disease is responsible for 35 percent of all breast
cancer-related deaths. While significant advances in understanding the
genomic drivers of primary TNBC have been made in the past decade,
relatively little is known about metastatic disease because surgical
tumor biopsies are rarely obtained from these patients.
For this new study, researchers completed what is believed to be the
largest genomic characterization of metastatic TNBC derived exclusively
from liquid biopsies. This was done by measuring cell-free DNA levels in
the blood—DNA that is excreted from both cancerous and normal cells
into the bloodstream. The study included blood samples from 164 women
with metastatic TNBC.
“Traditionally, we would need to obtain a tissue biopsy to perform
the whole genome sequencing tests that could reveal potential DNA-level
mutations driving a patient’s specific cancer. For metastatic breast
cancer patients, however, tissue biopsy can be risky or painful,” says Daniel Stover,
MD, co-first and co-corresponding author of the study and a breast
medical oncologist/researcher with the OSUCCC – James. “Being able to do
this type of genomic analysis from a simple blood draw allows us to get
a picture of a patient’s specific cancer genomic characteristics in a
less invasive way.”
Researchers then used a customized liquid biopsy technique they
developed to distinguish levels of DNA from cancer cells and healthy
cells (tumor fraction). Whole genome sequencing was performed to
identify potential mutations associated with metastatic TNBC.
The team found that 64 percent of patients had more than 10 percent
tumor DNA, and that this threshold of tumor DNA was correlated with poor
survival outcomes in patients with metastatic TNBC. Additionally,
researchers used genome-wide data to identify specific abnormal genes
more frequently altered in metastatic TNBC compared with primary cases
of the disease. These abnormal genes were associated with survival
outcomes in the metastatic TNBC patient population and could serve as
targets for new therapies for at-risk populations in the future,
researchers say.
“The recognition that a significant fraction of patients harbor
greater than 10 percent tumor DNA in blood suggests that liquid biopsies
may enable routine and non-invasive profiling of cancer genomes for
patients with metastatic TNBC,” says Viktor Adalsteinsson, PhD, co-corresponding author and group leader of the Blood Biopsy Team at the Broad Institute.
Researchers say this study suggests that minimally invasive liquid
biopsies could be used as a new predictive marker for metastatic TNBC.
“This is a very challenging disease. Our team’s findings — and others
enabled by liquid biopsy —could improve how we track disease and treat
our patients in the clinic,” says Heather Parsons,
MD, MPH, co-first author of the study and breast medical
oncologist/researcher at Dana-Farber Cancer Institute and Harvard
Medical School.
“These are exciting and important discoveries that could help us
understand how a patient’s cancer is likely to progress and, ultimately,
could have the potential to guide treatment decisions based on specific
genomic risk factors,” adds Stover, whose plans for his laboratory at
the OSUCCC – James include expanded validation studies with a goal to
bring this test into the clinic and investigate new methods to study
circulating DNA.
These findings will appear in the February 20, 2018, print issue of the Journal of Clinical Oncology. Stover
conducted this research while serving as an instructor of medicine at
the Dana-Farber Cancer Institute in Boston, in collaboration with the
Blood Biopsy Team at the Broad Institute and the Breast Oncology Group
at the Dana-Farber Cancer Institute.
Collaborators in this study include Gavin Ha, William Barry, Hao Guo,
Atish Choudhury, Melissa Hughes, Deborah Dillon, Ann Partridge, Nikhil
Wagle, Ian Krop, Eric Winer, Sara Tolaney and Nancy Lin of the
Dana-Farber Cancer Institute; J. Christopher Love of the Massachusetts
Institute of Technology; and Samuel Freeman, Gregory Gydush, Sarah Reed,
Gad Getz and Todd Golub of the Broad Institute.
Funding was provided by the Gerstner Family Foundation, Susan G.
Komen for the Cure, The Pink Agenda, Breast Cancer Research Foundation, V
Foundation for Cancer Research and National Cancer Institute.
Additional clinical research on liquid biopsy is underway with
current TNBC patients at the OSUCCC – James and Dana-Farber Cancer
Institute. To learn more about breast cancer treatment and research at
the OSUCCC – James, visit cancer.osu.edu/breastcancer.